1. Field of the Invention
This invention relates to a new microorganism Actinoplanacete sp., (MA 6559) ATCC No. 53771, which can produce the new immunosuppressant agents, "demethomycin" (L-682,993; also described as 31-desmethoxy-31-hydroxy-L-679,934) and "demethimmunomycin" (L-683,742: also described as 31-desmethoxy-31-hydroxy-L-683,590). The immunosuppressants are produced by culturing the microorganism, with L-679,934 or L-683,950, under conditions which demethylates the respective C.sub.31 methoxy group of L-679,934 or L-683,950.
2. Brief Description of Disclosures in the Art
In 1983, the U.S. FDA licensed cyclosporin, an extremely effective anti-rejection drug that revolutionized the field of organ transplant surgery. The drug acts by inhibiting the body's immune system from mobilizing its vast arsenal of natural protecting agents to reject the transplant's foreign protein.
As effective as the drug is in fighting transplantation rejection, it suffers drawbacks in causing kidney failure, liver damage and ulcers which in many cases can be very severe.
EPO Publication No. 0184162 to Fujisawa, hereby incorporated by reference, describes a new macrolide immunosuppressant FK-506 which is reputed to be 100 times more effective than cyclosporin. The macrolide is produced by fermentation of a particular strain of Streptomyces tsukubaensis. Also described is the closely related macrolide immunosuppressant FK-520, produced by S. hygroscopicus subsp. yakushimaensis.
U.S. Pat. No. 3,244,592 to T. Arai describes the culturing of Streptomyces hygroscopicus var. ascomyceticus to produce the antifungal "ascomycin".
There is, however, no description in the literature of the production of any immunosuppressive agents, which substantially lack the side effects of cyclosporin.
Newer, safer drugs exhibiting less side effects are constantly being searched for in the field.